1. Field of the Invention
The present invention relates to an excipient having high compactability and a process for preparing the same. More particularly, the present invention is concerned with an excipient having high compactability, comprising white powdery microcrystalline cellulose having an average degree of polymerization of from 100 to 375 and an acetic acid holding capacity of 280% or more, and having a specific compression characteristic. The present invention is also concerned with a process for preparing an excipient having high compactability, which comprises subjecting a cellulose material to hydrolysis with acid or oxidative degradation with alkali to form cellulose particles, subjecting the cellulose particles to purification to obtain aqueous purified cellulose particles, adjusting a water content of the aqueous purified cellulose particles to obtain an aqueous dispersion of the purified cellulose particles which has a solids content of 40% or less by weight, and subjecting the aqueous dispersion to heat treatment at 100.degree. C. or more, followed by drying. Furthermore, the present invention is concerned with an alternative process for preparing an excipient having high compactability, which comprises subjecting an aqueous dispersion of the purified cellulose particles which has a solids content of 23% or less by weight to thin film-forming treatment to obtain a thin film of the aqueous dispersion, followed by drying.
2. Discussion of Related Art
It is known that powdery materials are compressed into a shaped product in order to not only improve the handling characteristics of the materials but also impart desired functions to the materials. The most important required property of the compressed shaped product (usually, tablet) is a strength such that the compression-shaped product is unlikely to suffer abrasion or destruction during transportation and use thereof. When the tablet is used as a pharmaceutical product, in addition to the above-mentioned requirement of strength, the disintegration time of the tablet must be short so that the tablet can express a prompt pharmacological effect after the tablet is orally taken. Generally, after orally taken, a tablet is disintegrated in digestive tracts and then a pharmaceutical ingredient is dissolved in a digestive liquid. The dissolved ingredient is absorbed through walls of the digestive tracts, and dissolved in blood. The blood having the ingredient dissolved therein is circulated in a body to thereby express a pharmacological effect. Therefore, when a tablet disintegrates in digestive tracts immediately after orally taken, a rapid expression of the pharmacological effect of the active ingredient contained in the tablet can be obtained.
Most of powdery materials as such can hardly be processed into a shaped form even by compression. Therefore, it is necessary to blend a powdery material with an excipient having compactability and subject the resultant mixture to compression. For imparting a desired strength to a shaped product (tablet), it is necessary to determine (1) an appropriate amount of the excipient and (2) an appropriate compression force for compaction. Generally, the more the amount of the excipient and the larger the compression force, the higher the strength of the resultant tablet.
However, when it is desired that the content of a main ingredient (powdery material) in a tablet be high, for example, when the size of a tablet is required to be small as in the pharmaceutical industry, the quantity of an excipient is necessarily limited. On the other hand, an excessive compression force causes a tableting machine to be heavily loaded, leading to a wear of parts of the machine. Furthermore, when a tablet is produced by mixing film-coated granules and an excipient and punching the resultant mixture (such a tablet is called a granule-containing tablet), or when an enzyme or antibiotic is fabricated into a tablet form, it is necessary to form a tablet with a small compression force so as to prevent a damage on the film and a deterioration of the enzyme or antibiotic. Therefore, in producing a tablet, it is desired to use an excipient capable of exhibiting a high compactability with a small amount thereof.
As a conventional excipient which is used for the above-mentioned purpose, microcrystalline cellulose is known. Since the microcrystalline cellulose exhibits high safety, a relatively high compactability and a relatively excellent rate of disintegration, it is widely used in the pharmaceutical industry.
With respect to the microcrystalline cellulose, it is known that when microcrystalline cellulose having an average degree of polymerization of from 15 to 375, a bulk of from 7 to 34 lb/ft.sup.3 (1.84 to 8.92 cm.sup.3 /g) and an particle size of 300 .mu.m or less is used for producing pharmaceutical tablets, the tablets have an increased strength and an improved rate of disintegration (U.S. Pat. No. 3,146,168 corresponding to Examined Japanese Patent Application Publication No. 40-26274). It is also known that when microcrystalline cellulose having an average degree of polymerization of from 60 to 375, an apparent specific volume of from 1.6 to 3.1 cm.sup.3 /g, a tapping apparent specific volume of 1.40 cm.sup.3 /g or more, a ratio of a 200-mesh sieve residue of from 2 to 80% by weight and a repose angle of 35.degree. to 42.degree. is mixed with a main ingredient or an additive, the resultant powder mix has high flowability, and tablets made therefrom have an increased rate of disintegration (U.S. Pat. No. 4,159,345 corresponding to Examined Japanese Patent Application Publication Nos. 56-2047 and 56-38128).
With respect to a cellulose powder having compactability, it is known that a cellulose powder having an average degree of polymerization of from about 450 to about 650, an apparent density of from 0.40 to 0.60 g/cm.sup.3 (1.67 to 2.50 cm.sup.3 /g) in a compacted state and a ratio of a 200-mesh sieve residue of 50% or more by weight is suitable as excipient for forming tablets (Examined Japanese Patent Application Publication No. 51-17172). It is also known that a cellulose powder having a specific average diameter (30 .mu.m or less) and a specific surface area (1.3 m.sup.2 /g or more) exhibits high compactability (Unexamined Japanese Patent Application Laid-Open Specification No. 63-267731), that a cellulose powder having a specific crystalline form (type I), a sum of respective volumes of pores having a diameter of 0.1 .mu.m or more of 20% or more, based on the total apparent volume of the powder particles, and a ratio of a 350-mesh sieve residue of 90% or more by weight exhibits high flowability and compactability (Unexamined Japanese Patent Application Laid-Open Specification No. 1-272643), and that a cellulose powder having a crystalline form type I, a specific surface area of 20 m.sup.2/ g or more, a sum of respective volumes of pores having a diameter of 0.01 .mu.m or more of 0.3 cm.sup.3 /g or more, and a ratio of particles having a diameter of 100 .mu.m or less of 50% or more by weight exhibits high flowability and high compactability (Japanese Patent Application Laid-Open Specification No. 2-84401).
However, these conventional cellulose powders have a drawback in that the higher the compactability, the lower the rate of disintegration.
In general, for improving the compactability of a microcrystalline cellulose, it is effective to increase an apparent specific volume of the microcrystalline cellulose. For this purpose, attempts have been made to decrease the density of the microcrystalline cellulose particles by finely pulverizing microcrystalline cellulose (Unexamined Japanese Patent Application Laid-Open Specification No. 63-267731), or by rendering microcrystalline cellulose particles porous (Unexamined Japanese Patent Application Laid-Open Specification No. 2-84401). Since the product obtained in Unexamined Japanese Patent Application Laid-Open Specification No. 63-267731 is finely pulverized, the product naturally has a high apparent specific volume, and it has a low tapping apparent specific volume, so that it can be readily compacted to thereby give a tablet. However, a void space (water paths) within the tablet is decreased, so that the ability of the tablet to disintegrate is markedly deteriorated. On the other hand, the product obtained in Unexamined Japanese Patent Application Laid-Open Specification No. 2-84401 has extremely high specific surface area and high apparent specific volume because the particles of the microcrystalline cellulose have high porosity. However, such porous particles have a relatively low strength, so that the compression of the particles causes not only the particles to be adhered to one another, but also each particle to be deformed and become high in density. Therefore, the void space (water paths) within the tablet decreases, so that the ability of the tablet to disintegrate is markedly deteriorated.
As described above, conventional microcrystalline cellulose powders have drawbacks in that when the compactability of the microcrystalline cellulose powder is high, the rate of disintegration is low, whereas when the rate of disintegration is satisfactory, the compactability is low. That is, there is a serious technical dilemma.
Actually, although particularly in the pharmaceutical industry, an excipient is desired to have both a high compactability and an excellent rate of disintegration, excipients having a good balance of a compactability and a rate of disintegration have heretofore not been known.